Recall Mendel's two laws: Allele pairs separate during gamete formation and randomly unite when gametes fuse during fertilization. And each allele pair segregates independently during gamete formation. Decades after Mendel, researchers noticed that the behavior of chromosomes during egg and sperm development exactly matches Mendel's theory of inherited genes. This led them to propose the chromosome theory of inheritance.

This theory states that genes are located on chromosomes, which undergo segregation and independent assortment. Thomas Hunt Morgan provided support for the chromosome theory of inheritance with his work using the fruit fly Drosophila melanogaster.

Drosophila are good for genetic studies because they are easy to breed, each female can produce hundreds of offspring, and it only takes around 12 days to go from an egg to an adult fly. Also, Drosophila chromosomes are easy to see under the microscope.

Flies have three pairs of autosomes and one pair of sex chromosomes. A sex chromosome is a chromosome that determines the sex of an individual, and an autosome is any chromosome that is not a sex chromosome.In general, Drosophila females have two X chromosomes, while males have one X chromosome and one Y chromosome.

Most of the flies Morgan looked at had red eyes. Since this is the phenotype of the majority of individuals in a natural environment, it is called the wild-type phenotype. One day, Morgan found a white-eyed fly! The characteristic of white eyes is a mutant phenotype, since it’s caused by a mutation of the wild-type gene.

Morgan’s white-eyed fly was male. He mated the white-eyed male with a red-eyed female, and all of the F1 offspring had red eyes. This suggests that the red-eye allele is dominant to the white-eye allele. However, when the F1 siblings were crossed with each other, all of the F2 females had red eyes, while 50% of the males had red eyes and 50% had white eyes. Because the gene was inherited differently in males and females, Morgan proposed that this eye color gene is on the X chromosome. Let's use Punnett squares to see how he reached this conclusion.

We'll use big R to represent the red-eye allele, and small r to represent the white-eye allele. Let's look at what offspring we'd see if the eye color gene is on an autosome or on the X chromosome. Let’s presume that Morgan’s wild-type females were homozygous for the dominant allele.

If the gene is on an autosome, the white-eyed male would have to be homozygous for the recessive allele. If the gene was on the X chromosome, a white-eyed male would have the recessive allele on his X chromosome. Since chromosomes separate during meiosis and randomly unite during fertilization, we’d expect red-eyed females and males in the F1generation in either case. At this point, we can't tell where the gene is located.

When the F1 offspring are crossed with each other, if the gene is on an autosome, we'd expect a 3 to 1 ratio of red-eyed to white-eyed flies in the offspring. And we'd expect to see equal numbers of white-eyed males and females due to random assortment. This is not what Morgan saw.

On the other hand, if the gene is on the X chromosome, we’d expect only red-eyed F2 females, 50% red-eyed males, and 50% white-eyed males. This is precisely what Morgan saw. Morgan’s results suggested that genes and chromosomes are directly associated.

Since there are fewer chromosomes than genes, each chromosome must contain many genes. Genes located on the same chromosome may not assort independently during meiosis. Genes that are inherited together more frequently than would be expected from their independent assortment in meiosis are called linked genes. The greater the distance between two genes, the more likely it is that a crossover event will occur between them.

Morgan looked at linked genes in Drosophila. He did an experiment looking at two genes on an autosome, an eye color gene and a body color gene. The eye color gene in this experiment is different from the X-linked eye color gene we looked at earlier.

This red-eye allele, which we'll call big P, is dominant to the purple-eye allele, small p. And the brown-body allele, big B, is dominant to the black body allele, small b.

He crossed doubly homozygous dominant wild-type flies with doubly recessive purple-eyed, black-bodied flies to get doubly heterozygous F1 flies. If no crossovers occur between the two genes, then crossing the F1 flies to doubly recessive purple-eyed, black-bodied flies should give 50% wild type and 50% purple-eyed, black-bodied offspring. These two offspring classes are called parental types, since they inherited intact parent chromosomes.

Instead, Morgan observed 47% wild-type offspring, 47% black-bodied, purple-eyed, 3% black-bodied, red-eyed, and 3% brown-bodied, purple-eyed, indicating that some recombination of the chromosomes had occurred. Recombination is the formation of new combinations of alleles along a chromosome by crossing over.

Two of the classes of offspring are parental types. The other two are called recombinants, since they resulted from recombination. We can use the fraction of recombinant offspring to describe the distance between the two genes.

A map unit is a unit used to measure distances between genes. The number of map units between two genes is equal to the crossover percentage between the genes. Since 6% of Morgan’s F2 offspring were recombinants, the two genes are 6 map units apart.

Only map distances shorter than 50 map units directly reflect crossover frequencies. For two genes 50 map units apart, there’s a 50% chance that a crossover will occur between them, so there’ll be 50% parental type and 50% recombinant offspring in a 1:1:1:1 ratio of possible allele combinations. This same ratio would occur if the genes were on different chromosomes and assorted independently. Genes that are 50 or more map units apart are therefore considered unlinked, even if they’re on the same chromosome. Crossover frequencies greater than 50% are never observed.

Why didn’t Mendel observe crossover offspring? The 7 pea traits he studied were either on different chromosomes, or were greater than 50 map units apart. Morgan’s crossover studies in Drosophila paved the way for linkage mapping in other organisms. A linkage map, or genetic map, is a diagram of the order of genes along a chromosome, including the distance between the genes. To learn about how linkage data can be used to make genetic maps, see the Reference Sheet.

Copyright 2006 The Regents of the University of California and Monterey Institute for Technology and Education